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Balancing Real-World Data Quality vs. Locality in Supporting Single-Arm HTA Submissions


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Walking a Tightrope: How to Balance Real-world Data Quality vs. Locality in Supporting Single-arm HTA Submissions?

Cytel moderator: Grammati Sarri



Innovative health technologies, precision medicine, and the increasing recognition of real-world evidence (RWE) have transformed the healthcare decision-making process. To follow these trends and to meet a high need for earlier patient access to promising technologies, the clinical trial landscape is rapidly evolving with the rise of single-arm trials. To establish comparative effectiveness of new technologies, decision-makers have shown preference for national data to construct external control (EC) arms reflecting local treatment pathways with an emphasis on patient representativeness. However, this preference is not always realistic depending on data availability, sample size, and quality that may affect confidence in results and, ultimately, in decision-making. Can the advance in RWE methodological approaches overturn the HTA over-dependency on local data?



Unquestionably, the selection of EC arms to support the comparative effectiveness analyses for health technologies evaluated in single-arm trials has been a major area of criticism during HTA submissions. The moderator will begin by framing the topic, conflicting issues around quality and locality in the selection of the most reliable source for RWE EC, and the impact of under-development HTA guidance. Then, the moderator will present three case studies in different disease areas (rare diseases, oncology, chronic conditions) to the panel, who will debate, from industry, academic, and HTA perspectives, the main drivers for RWE EC acceptance and challenges when decision-makers are urged to select the least-biased RWE source to support reimbursement submissions. How challenging is it to walk the line between RWE quality and locality when selecting the “most appropriate” EC arm? Which factors may shift the decision from one side (quality) to the other (locality), and is this disease-dependent? An interactive discussion using an online polling system with the audience will be encouraged. Industry, researchers, and payers will benefit.


We asked moderator Grammati Sarri, Senior Research Principal, RWA Health Economics, to share her insight on this upcoming panel discussion:


What motivated you to explore this topic and why is this moment significant? What are the stakes of the questions being explored?

A door has opened for HTA agencies to integrate RWE into reimbursement decision-making. NICE and CADTH are among the first to introduce guidance regarding the incorporation of such evidence in clinical and cost-effectiveness submissions. However, we are now seeing an increase in HTA submissions that rely on single-arm trials, and the selection of the most appropriate source of evidence to construct external control arms—most commonly RWE—is crucial. The process behind this selection, though, is far from straightforward; so far, HTA bodies have considered locality of RWE as one of the key drivers for the acceptance of the source of external control data in single-arm trial submissions. But what kind of trade-offs in RWE quality are decision-makers willing to accept when local data is the preference? What can we leverage from the new methodological advancements in the RWE landscape such as trial emulation, frameworks for ensuring trustworthy combinations of RCTs and RWE, and bias quantification methods? Our panel will discuss these issues using three case-study examples in different disease areas (i.e., rare diseases, oncology, and chronic conditions) to explore whether there are context-specific challenges and considerations when trade-offs are made between locality vs. RWE quality.

How is Cytel positioned in this work? What can we offer our clients regarding this topic?

Cytel has demonstrated leadership in causal inference methods (e.g., in trial emulation, bias quantification methods, and synthetic controls) with high-impact publications, developing methodological standards and leading international efforts with key collaborators from HTA agencies and the pharmaceutical industry to test these methodologies using real cases. Most importantly, our team has extensive experience in supporting single-arm HTA submissions through clinical and cost-effectiveness analysis; therefore, we can anticipate what potentially mitigating strategies can be successful for these products aiming to enter the market. Finally, let’s not forget that some of the Cytel team have worked for HTA agencies, giving many of us an inside look at the HTA process. Contact us to learn more.


Cytel will be represented at over 60 presentations at ISPOR Europe 2022, with more issue panels and workshops than any other participating organization. To download the full Cytel program, click below. We look forward to seeing you there!


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